PROOF 301
A Phase 3 Multicenter, Open-Label, Randomized, Controlled Study of Oral Infigratinib Versus Gemcitabine With Cisplatin in Subjects With Advanced/Metastatic or Inoperable Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations: The PROOF Trial
Phase 3N = 48NCT03773302
- Population
- Adults with unresectable, locally advanced or metastatic cholangiocarcinoma with an FGFR2 gene fusion or other rearrangement, no previous systemic therapy for advanced disease (gallbladder and ampullary carcinoma excluded; a protocol amendment allowed up to one cycle of gemcitabine-based chemotherapy).
- Design
- Open-label, randomised (2:1) phase 3 trial of infigratinib 125 mg on days 1-21 of 28-day cycles versus gemcitabine 1,000 mg/m2 plus cisplatin 25 mg/m2 on days 1 and 8 of 21-day cycles, stratified by disease stage, region, prior neoadjuvant or adjuvant treatment and one prior cycle of gemcitabine-based chemotherapy. Primary endpoint: progression-free survival by blinded independent central review (BICR). Terminated early by the sponsor because of poor accrual (the paper's reason; the registry record gives the sponsor's discontinuation of infigratinib development in oncology): 1127 patients were pre-screened and 48 randomised against a target of about 300. The report states that inferential statistical analyses could not be carried out.
- Primary endpoint
- PFS
- Arms
- Gemcitabine plus cisplatin (control, n = 19): Gemcitabine 1,000 mg/m2 plus cisplatin 25 mg/m2 on days 1 and 8 of 21-day cycles
- Infigratinib (experimental, n = 29): Infigratinib 125 mg orally on days 1-21 of 28-day cycles
- People
- Abou-Alfa GK
Δ median PFS−0.6 monthsΔ ORR+22.1 points
Show the numbers
| Endpoint | Analysis | Infigratinib | Gemcitabine plus cisplatin | Effect |
|---|---|---|---|---|
| PFSITT: all randomised patients (48) | primaryAbou-Alfa 2026 | median 7.4 months | median 8 months | Assessed by blinded independent central review. The full text gives 95% confidence intervals of 5.4 months to not evaluable (infigratinib) and 3.4 months to not evaluable (chemotherapy) and no hazard ratio. Terminated early for poor accrual; descriptive only. |
| ORRITT: all randomised patients (48) | primaryAbou-Alfa 2026 | 37.9% (20.7–57.7%) | 15.8% (3.4–39.6%) | By blinded independent central review; all responses were partial responses. The abstract gives the two response rates without intervals. |
| Endpoint | Analysis | Infigratinib | Gemcitabine plus cisplatin | Effect |
|---|---|---|---|---|
| PFSITT: all randomised patients (48) | primaryAbou-Alfa 2026 | median 7.4 months | median 8 months | Assessed by blinded independent central review. The full text gives 95% confidence intervals of 5.4 months to not evaluable (infigratinib) and 3.4 months to not evaluable (chemotherapy) and no hazard ratio. Terminated early for poor accrual; descriptive only. |
| ORRITT: all randomised patients (48) | primaryAbou-Alfa 2026 | 37.9% (20.7–57.7%) | 15.8% (3.4–39.6%) | By blinded independent central review; all responses were partial responses. The abstract gives the two response rates without intervals. |
- Infigratinib (experimental)
- Gemcitabine plus cisplatin (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Infigratinib | Gemcitabine plus cisplatin |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 5 | 62.6% | 64.8% |
| 10 | 39.2% | 42.0% |
| 15 | 24.5% | 27.3% |
| 20 | 15.4% | 17.7% |
Appears in
Sources
Abou-Alfa GK, Borbath I, Roychowdhury S, Goyal L, Lamarca A, Macarulla T, et al. Phase III trial of infigratinib versus gemcitabine/cisplatin in adults with advanced cholangiocarcinoma with FGFR2 gene fusion or rearrangement: results and reflections on early termination of PROOF 301. ESMO Open. 2026;11(4):106306.